Targeting CD4⁺ Cells with Anti-CD4 Conjugated Mertansine-Loaded Nanogels

Abstract

CD4⁺ T lymphocytes play an important role in controlling many malignancies. The modulation of CD4⁺ T cells through immunomodulatory or cytotoxic drugs could change the course of disease progression for disorders such as autoimmunity, immunodeficiency, and cancer. Here, we demonstrate that anti-CD4 conjugated polymeric nanogels can deliver a small molecule cargo to primary CD4⁺ T cells and a CD4^high T cell lymphoma. The antibody conjugation not only increased the uptake efficiency of the nanogel (NG) by CD4⁺ T cells but also decreased the non-specific uptake of the NG by CD4^- lymphocytes. For T lymphoma cell lines, the mertansine-loaded conjugate displayed a dose-dependent cell growth inhibition at 17 ng/mL antibody concentration. On the other hand, antibody-drug conjugate (ADC)-type formulation of the anti-CD4 reached similar levels of cell growth inhibition only at the significantly higher concentration of 1.8 μg/mL. NG and antibody conjugates have the advantage of carrying a large payload to a defined target in a more efficient manner as it needs far less antibody to achieve a similar outcome.